We are using quantitative immunochemical methods to locate the antigenic determinants on hemoglobins A and S. We have changed the metal in the porphyrin of the heme group in both hemoglobins and are studying these reconstituted hemoglobins by quantitative precipitin and radioimmunoassay to see if any significant conformational changes have been induced. This project will be expanded to chemical modification of certain amino acid residues and various enzymatic cleavages to test the effects of these procedures on the binding of antibodies against the native proteins. These studies will allow us to detect subtle changes in the conformation of hemoglobins with zinc, copper, cobalt, manganese and nickel metalloporphyrins. Further, the metalloporphyrin and the chemical modification studies should allow us to locate antigenic determinants on the hemoglobin molecule. In addition we are studying the effects on the gelation of sickle hemoglobin of the metalloporphyrin substitutes.